title: Cigarette smoke extract induces thymic stromal lymphopoietin expression, leading to T(H)2-type immune responses and airway inflammation.
abstract: BACKGROUND
  Both active and passive smoking are considered to be risk factors for asthma development. However, the precise mechanisms involved remain elusive. Recently, thymic stromal lymphopoietin (TSLP) has been shown to play a key role in the development of T(H)2-type allergic inflammation in patients with asthma.
  
  
  OBJECTIVE
  The aim of this study was to investigate whether there was a causal relationship between cigarette smoke exposure and TSLP expression in the lung.
  
  
  METHODS
  We examined the effects of repeated intranasal exposure of cigarette smoke extract (CSE) on TSLP mRNA and protein expression in the mouse lung by means of real-time PCR, Western blotting, and immunohistochemistry. We also examined the effects of intranasal exposure of CSE plus ovalbumin (OVA) on T(H)2-type immune responses and lung pathology.
  
  
  RESULTS
  Repeated exposure of CSE induced TSLP mRNA and protein expression, which was inhibited by treatment with antioxidative N-acetylcysteine and by TNF-alpha receptor I deficiency. In addition, the intranasal exposure of CSE simultaneously with OVA induced OVA-specific T(H)2-type immune responses and airway inflammation, which were inhibited by the blockade of the TSLP activity.
  
  
  CONCLUSIONS
  CSE induced TSLP expression in the mouse lung in an oxidative stress-dependent and TNF-alpha receptor I-dependent manner, and when challenged simultaneously with an antigen, CSE promoted the development of airway inflammation in association with T(H)2-type immune responses.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyata
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohba
authors.forename: Takashi
authors.initials: T
authors.lastname: Ando
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Hatsushika
authors.forename: Fumiko
authors.initials: F
authors.lastname: Suenaga
authors.forename: Naomi
authors.initials: N
authors.lastname: Shimokawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohnuma
authors.forename: Ryohei
authors.initials: R
authors.lastname: Katoh
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D045424:Complex Mixtures / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D045424:Complex Mixtures; D016207:Cytokines; D016166:Free Radical Scavengers; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014028:Tobacco Smoke Pollution; D000111:Acetylcysteine; D000094632:Thymic Stromal Lymphopoietin